Abstract: SA-PO115
NADPH-Oxidase NOX5 Aggravates Renal Injury in Akita Mouse Model of Diabetic Nephropathy
Session Information
- Diabetic Kidney Disease: Basic - III
October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Diabetic Kidney Disease
- 601 Diabetic Kidney Disease: Basic
Authors
- Jha, Jay Chandra, Monash University, Melbourne, Victoria, Australia
- Cooper, Mark E., Monash University, Melbourne, Victoria, Australia
- Kennedy, Chris R., Kidney Research Centre, Ottawa, Ontario, Canada
- Touyz, Rhian, Glasgow University, Glasgow, GLASGOW, United Kingdom
- Jandeleit-Dahm, Karin, Monash University, Melbourne, Victoria, Australia
Background
Renal reactive oxygen species (ROS) play an important role in mediating kidney injury in diabetes. Increasing evidence suggests that the pro-oxidant enzyme, Nox5 plays a significant role in human diabetic nephropathy (DN). Nox5 is present in humans and rabbits but not in mice or rats. Thus, there is a paucity of information about Nox5 in conventional animal models of DN. We examined the role of Nox5 in the insulin deficient diabetic Akita mice model using human inducible transgenic mice that express Nox5 selectively in endothelial cells (VEcad+Nox5+) or in mesangial cells (SM22+Nox5+). We also examined the endogenous expression of Nox5 in a high fat fed rabbit model of kidney disease.
Methods
At week 10 mice were culled and kidneys were removed for the assessment of structural damage as well as gene and protein expression of markers of inflammation, fibrosis and oxidative stress. Protein expression of Nox5 and its localization in glomerular cells (endothelial and mesangial cells) were examined in transgenic mice by immunostaining. We also examined expression of pro-fibrotic gene in high fat fed rabbits by next generation sequencing (NGS) and RT-PCR and renal injury by histochemistry
Results
Expression of Nox5 was confirmed in glomerular endothelial and mesangial cells of transgenic mice. Diabetes induced increase in glomerulosclerosis, gene and protein expression of fibronectin and MCP-1 as well as nitrotyrosine were further increase in both diabetic Nox5 transgenic mice. Moreover, increased expression of Nox5 in high fat fed rabbits versus normal diet fed rabbits was associated with increased expression of fibronectin, CTGF, collagen IV and VCAM-1 as well as increased mesangial expansion in the kidney.
Conclusion
These findings in both transgenic mice model (endothelial and mesangial cells) suggest that Nox5 plays a significant role in mediating renal injury in diabetes.